1. Field of the Invention
The present invention relates to antimicrobial ophthalmic compositions and methods for their use. The compositions may be, for example, ocular treatment compositions or ocular lens care compositions having a polyquaternary ammonium and an amidoamine having at least one alcohol group.
2. Description of Related Art
The eyes are one of the most sensitive externally-exposed organs. As a result of this sensitivity or in response to degradation, the eyes may require treatment (e.g., for dry eye or infection or corrective surgery or corrective lenses). Some of these treatments include directly applying a composition to the affected eye in order to ameliorate the condition (e.g., for dry eye or infection). For treatments requiring a lens that will directly contact the eye, a composition may be needed, for example, to store, condition, rinse, or reduce the microbial load on the lens. Most, if not all, of the compositions used for eye or lens treatment require an additive with antimicrobial, disinfective, and/or preservative capabilities. Since this antimicrobial/preservative will come into contact with the eye (either directly or via a lens), the antimicrobial/preservative should cause minimal ocular irritation or user discomfort. Many antimicrobials have been developed for ophthalmic use.
Antimicrobials for contact lens care are one type of ophthalmic antimicrobial. Contact lenses generally fall into three categories: hard lenses formed from materials prepared by polymerization of acrylic esters, such as polymethyl methacrylate (PMMA); rigid gas permeable (RGP) lenses formed from silicone acrylates and fluorosilicone methacrylates; and, soft type lenses that may be formed from traditional copolymers such as 2-hydroxyethyl methacrylate (HEMA) or from newer silicon-containing hydrogel materials. Examples of extended wear high vapor diffusion soft contact lenses include, but are not limited to, those made from silicon-containing hydrogel materials (silicone hydrogels), such as the Focus® NIGHT & DAY™ lenses from CIBA Vision (Atlanta, Ga.), and those made from Balafilcon® A, such as PUREVISION® lenses from Bausch & Lomb, Incorporated (Rochester, N.Y.).
Contact lenses typically are cleaned to remove any accumulated buildup and disinfected to kill harmful microorganisms that may be present or grow on the lenses. However, ocular tissues may be adversely impacted during contact lens wear due to exposure to preservatives, disinfecting agents, cleaning agents, and other components contained in contact lens care solutions. Exposure may occur through direct tissue contact with a solution or indirect contact with a solution that may have adsorbed or absorbed to the contact lens during cleaning/disinfection and subsequently is desorbed into the eye during contact lens wear.
Hard or rigid lenses have a lower tendency to bind ingredients used in contact lens care compositions since they possess low vapor diffusion and absorb only minor amounts of aqueous fluids. On the other hand, due to their purposely designed high rate of oxygen transmission, soft lenses have a greater tendency to bind contact lens solution ingredients. In addition, since they tend to be worn for longer periods of time, soft contact lenses also have greater opportunity to desorb any bound ingredients. These desorbed materials (e.g., antimicrobial agents) may lead to, for example, ocular irritation or discomfort. Therefore, developing lens care solutions for soft contact lenses poses particular challenges.
Many multi-purpose solutions that may be used to clean, disinfect and wet contact lenses, followed by direct insertion into the eye, are available. Multi-purpose solutions must be strong enough to kill harmful microorganisms that may be present or grow on the lenses while being gentle enough to use on the eyes. Such a solution also must be compatible with the many contact lens materials, including the silicone hydrogel materials. Measures of contact lens compatibility include contact lens discoloration, physical parameter change, fragility, and uptake/release of solution components, especially antimicrobial agents. Contact lens care solutions, such as a multi-purpose solutions (MPSs), attempt to balance cleaning and disinfection ability with safety and comfort on the eyes. The addition of more effective disinfecting agents usually has the effect of reducing contact lens material compatibility or ocular comfort of the solution. One way to achieve additional material compatibility and comfort is to reduce the amount disinfecting agent. However, conventional knowledge dictates that this results in lower antimicrobial efficacy.
The U.S. Food and Drug Administration (FDA) requires contact lens solutions to meet certain biocidal performance criteria against specified representative bacteria and fungi set in the Premarket Notification (510 k) Guidance Document For Contact Lens Care Products, Appendix B, Apr. 1, 1997 and ISO/FDIS 14729: Ophthalmic optics-Contact lens care products—Microbiological requirements and test methods for products and regimens for hygienic management of contact lenses, January 2001. These guidance documents are also known as the “stand-alone” disinfection standard. A contact lens solution that qualifies as a “Chemical Disinfecting Solution” is one that does not require rubbing to meet biocidal performance criteria known as the “Stand Alone Standard.” A contact-lens solution that qualifies as a “Chemical Disinfecting System” is one that requires rubbing to pass biocidal performance criteria known as the “Regimen Standard.” The FDA and ISO guidelines for both disinfection efficacy standards follow.
Stand-Alone Disinfectant (Primary) Criteria:
Average Log Reduction atOrganismLabeled Soak TimeS. marcescens, ATCC 138803.0 logsS. aureus, ATCC 65383.0 logsP. aeruginosa, ATCC 90273.0 logsC. albicans, ATCC 102311.0 logF. solani, ATCC 360311.0 log
Regimen-Dependent Disinfectant (Secondary) Criteria:
Average Log Reduction atOrganismLabeled Soak TimeS. marcescens, ATCC 13880Minimum of 1.0 log per bacteriumS. aureus, ATCC 6538Sum of all three bacteria log-dropsP. aeruginosa, ATCC 9027Greater than or equal to 5.0 logsC. albicans, ATCC 10231StasisF. solani, ATCC 36031Stasis
For additional cleaning and comfort, some practitioners and companies recommend that rubbing be used in conjunction with a solution which is approved as a stand-alone disinfectant.
As may be deduced from the relatively lower biocidal requirements, Candida albicans and Fusarium saloni are the most antimicrobial agent resistant of the five representative bacteria and fungi. As a result, achieving adequate antimicrobial activity against Candida and Fusarium often is a difficult task when designing an antimicrobial component for a particular contact lens care solution. There is a need for an antimicrobial component that exhibits higher biocidal effect on Candida and Fusarium, even when used in relatively small amounts.
Aside from the FDA-specified representative bacteria and fungi, Acanthamoeba is another organism that is resistant to most antimicrobial agents. A recent increase in cyst-type Acanthamoeba infection among contact lens wearers in the U.S. indicates a need for an antimicrobial component that exhibits higher biocidal effect on Acanthamoeba. While it is known that alexidine is very biocidal against trophzoite and cyst-type Acanthamoeba, it is not very biocidal against Fusarium. There is a need for an antimicrobial component with broader biocidal efficacy.
U.S. Pat. No. 7,025,958 discloses the use of amidoamines for treating and preventing Acanthamoeba-related and fungal infections. The patent examples incorporate 5 ppm myristamidopropyl dimethylamine (MAPD) into Opti-Free® RepleniSH® multipurpose contact lens solution (Alcon, Inc., Fort Worth, Tex.). One disadvantage of using amidoamines in a contact lens care composition is that it has a strong tendency to adsorb onto various types of ocular lenses. As discussed above, this may lead to eye irritation after the contact lens is placed in the eye and the antimicrobial agent desorbs from the contact lens. The amidoamines disclosed in the patent also may not have a long shelf life since they may gradually migrate out of the solution to the inside wall of the plastic container. Over time, the loss of antimicrobial agent from the solution may lead to significant loss in antimicrobial efficacy.
There is need for an ophthalmic antimicrobial that exhibits broad and strong biocidal efficacy while causing minimal ocular irritation or user discomfort. The present invention addresses this need by providing an antimicrobial having two antimicrobial agents that, when combined, surprisingly have synergistic biocidal efficacy, even against more antimicrobial agent resistant microorganisms.